Tuesday, August 4, 2015

Metabolic Lessons from Anorexia Nervosa

But something else, that's seemingly always a hot topic when calories are discussed, is this concept of metabolic adaptation. Quite often this gets referred to as having a "damaged metabolism". I'm just going to use that term (and w/o quotes), and don't mean to imply that it is necessarily appropriate or justified, just that it's easier than explaining it repeatedly. The damaged metabolism is thought to develop from frequent, chronic, and/or severe calorie restriction. The mechanism is that the body down-regulates basal metabolic rate such that a 150 lb person who has dieted down from 250 lbs will require fewer calories to maintain that weight compared with a person whose normal, stable weight is 150 lbs.

The opening sentence was interesting from a Carb-Sane Asylum point of view:

Anorexia nervosa is a condition in which
severe voluntary restriction of carbohydrate
intake, and in some cases restriction of consumption
of all foods, results in weight loss.

I guess this is evidence that Gary Taubes was right after all, everyone knew it was carbohydrate that made you fat before the 1977 Committee turned the spotlight onto fat. Ahhh, but not so fast, because anorectics in the 80's became generally fat phobic -- primarily because of calories -- and there has been no indication that "success" rates for becoming anorexic declined as a result. [/snarkasm] , please forgive, I know this is a serious subject.

Onward to the study!

Frequently,
the anorectic is previously obese
and, in this case, it is clinically expedient to
be able to predict, and control, the rate of
weight gain in order to give the patient confidence
that she will not, once more, become
overweight.

I'm not sure how frequently truly obese people develop anorexia. In my reading, I've found that most of the accounts of anorectics -- for example in books like Hilde Bruch's The Golden Cage -- tend to begin as normal to slightly overweight individuals. And yet it is interesting that severe calorie restriction (often accompanied by excessive exercise) is a "successful" formula for becoming extremely underweight regardless of starting point. If all of the metabolic adaptations and such we are told and warned about truly conspired to prevent weight loss past a certain point, this should not be the case.

I would note that the researchers defined previously obese as weighting 20+% over ideal weight prior to onset of anorexia. Even taking the highest target refeed weight for these subjects of 60 kg, that equates to 132 lbs. Worst case scenario, then, would make weighing 158 lbs or more their definition of obese. Whether this may meet some technical threshold, even 30 lbs overweight is not what many are dealing with when we're talking obesity and weight loss. So let's keep that in perspective as we're not provided any information as to how overweight or obese these eight subjects were. Continuing ...

The purpose of this study
was to investigate some of the phenomena
that may be related to the rate of weight
gain, especially in the light of recent reports
(3-6) that there is an increase in the thermic
effect of a meal in infants recovering from
malnutrition and that when the recovery
growth is most rapid the postprandial metabolic
rate is greatest.

There are a lot of books and programs out there for fixing your metabolism, recovering from dieting, or so-called reverse dieting, that either rely heavily on, or are entirely based on anorexia recovery research ... like this study. In my opinion, it is irresponsible of many authors to cite such research without stressing the unique situation of the established anorexic:

Very low body fat

Extreme underweight

Altered hormonal and neurochemical state

Important because weight gain is to re-establish normalcy from a state of deficiency. Employing the same strategies starting from normalcy or surplus makes no sense at best, or can be detrimental at worst.

Severe calorie restriction

Malnutrition (micronutrients, etc.)

Electrolyte imbalance, etc.

Such a body is likely to react differently to refeeding than, say, that of a 150 lb person who has dieted down from 250 lbs. And yet, in-patient "recovery" from anorexia can be fairly predictably achieved. Notice the quotes there, as recovery from this disorder involves far more than re-establishing a normal weight for stature.

This study involved 15 hospitalized patients with varying degrees of anorexia, you can view the details yourself as my link is to the full text. The underweight subjects were re-fed during a period of "complete bedrest". The refeed diets were the same for all subjects, calories averaged 2800/day (2500-3000 range) of roughly 14% protein, 36% fat and 50% carbohydrate.

Weight Regain

One interest of the researchers, was whether or not the rates of regain were different between those subjects who were previously obese (PO) and those who were not (NO). The subjects were refed and were weighed periodically. The weight gain trajectories are plotted for individual subjects which gives us a much better idea of what is going on than any means. The small image (as always click to enlarge) is the full plot from the study with the PO on top/bold and NO on the bottom. What caught my eye was the slopes of the curves which appear to be similar both within each plot and between them. So I overlayed the two, shown below.

There really does not appear to be any pattern of difference in the regain trajectories. However working with averages, the researchers noted greater weight gain in each of the 10 day periods (first 10, second 10, last 10 before reaching target) in the PO vs. the NO groups though differences in these intervals did not rise to the level of statistical significance. Over the full refeed period, the PO averaged gains of 187 g/day (0.412 lb/day) vs. NO averaging 148 g/day (0.326 lb/day), which was statistically significant to p= 0.01. I'm not sure how much I put into these averages or differences between them due to the small sample size (15 subjects, 8 PO, 7 NO) and variation in time of admission, degree of underweight, etc.

From the Discussion:

It is necessary to consider three possible
reasons why the previously obese anorectic
patients gained weight more quickly than
the previously nonobese patients.

1. They ate more food.

2. They had lower metabolic rates
throughout the day.

3. They had a lower thermic response to
food.

It is possible, but because of the strict
supervision of the patients, unlikely, that
the PO patients ate more food than the NO.
It is impossible to compare directly the
gross energy expenditure (kcals/h) of the
two groups because they were not identical
nor were they matched for degree of emaciation
when the measurements were made.

As you can see, reason #1 was ruled out due to it being a metabolic ward study, but since intake wasn't standardized to starting weight, weight deficit or energy expenditure, it makes any weight-gain-per-surplus-calorie measure impossible. So they measured both resting energy expenditure and thermic response to a 100 gram glucose load to investigate reasons #2 & #3.

Resting Metabolic Rates - Premeal

The analysis of resting metabolic rates was accomplished by dividing the subjects into two "treatment" groups:

Early Treatment: Grossly underweight (15 to
42%) , Refed ≤ 34 days

Late Treatment: Within 10% of target weight , Normal diet ≥ 4 weeks.

Subjects ate breakfast (time not specified) then fasted until 1pm. The results from Early to Late treatment, in anorectics

Although the premeal metabolic rate of
the late treatment group as a whole was
lower (P < 0.001) than that of the control
group - both in gross terms and when related
to surface area - there was no significant
difference between the premeal metabolic
rate of the late treatment NO group
and the controls. Oddly, nothing more said about PO group but if all late treatment averaged lower, and there was no difference between the NO subset, this implies that the PO subset had lower pre-meal RMR. Significant? Guessing not.

Two points I'd like to stress:

Despite severe caloric restriction resulting in anorexia, once the group got back close to target weight, there was no damaged metabolism.

Metabolic rates were no different than those who weighed the same but with no history of anorexia.

In other words: no lingering metabolic damage in the anorexics who began at a normal weight.

It should be noted that these RMRs were not what is usually measured, which is at rest in the morning before eating or drinking anything. Thus, as noted by the researchers, are not directly comparable to this measure that they designate as BMR. Comparing the pre-meal RMRs to BMRs reported in a study of a most similar population:

Controls were 20% higher

Refed anorexics were 4% higher

The 5 Subjects tested within 3 days of admission were 24% below the standard for a person of the same age, height and target weight.

So obviously the pre-meal RMR includes some general activity and residual food thermogenesis. The swing from -24 to +4 percent is considerable. Still, does it come all the way back? Were the controls confined to an equal stay of "total bedrest"? If not, this could explain most of the difference. Even though activity per se doesn't alter basal metabolism, total bedrest "metabolism" does change. I'll see if I can track that down at some future date, but if anyone has any relevant studies, you know the drill!

As regards the initial state of the anorexics metabolic rate, from the discussion:

Therefore roughly one-third of the depressed metabolic rate is due to surface area and two-thirds is due to metabolic adaptation.

These deficits may be even greater since the comparisons are midday RMR vs. BMR estimates.

They then compare this to Ancel Keys' infamous Minnesota Starvation Experiment where he saw roughly 40% reduced metabolic rate in his intentionally starved men, roughly 30% when adjusted for surface area, and a 20/80 split for surface area vs. adaptation accounting. In addition to possible gender differences, some other factors might be in play here such as more consistent deficit in MSE, length of restriction in anorexia, etc.

Looking at just the 5 recently admitted patients, 2 PO, 3 NO

PO: RMR deficit was 21% overall, 11% vs. surface area

NO: RMR deficit was 26% overall 18% vs. surface area

From this the reduction in RMR vs. BMR standards for newly admitted anorectics was roughly 50:50 surface area and metabolic adaptation. I'm not sure what to make of this to be honest. It seems more an accounting of the evidence with no real attempt to explain it.

Thermogenic Response to Glucose

Next they administered a "glucose meal" of 100g glucose solution. This was in place of the midday meal at 1pm. Energy expenditure was measured for 2½ hours afterwards. I've summarized the results below, all averages:

All anorectics 16% increase in metabolic rate

Controls only experienced a 5% increase in metabolic rate

The difference between anorectics and control was statistically significant.

PO group experienced a 14% increase in metabolic rate vs. 19% for the NO group.

The difference between PO and NO was not statistically significant.

The early treatment group experienced a 14% increase in metabolic rate vs. 16% for the late treatment group.

The difference between early and late treatments was not statistically significant.

During the 2½ hours, the total calories expended were:

19 kcal for anorectics vs. 8 kcal for controls

18 kcal for PO vs. 21 kcal for NO

15 kcal for early treatment vs. 23 kcal for late treatment

Only the difference between anorectics vs. controls was statistically significant.

I should point out that I came across this study looking into the thermogenic component of exercise in anorexics and through another study. I only mention this because when one looks at lean and obese people, it is generally the lean that have a higher thermogenic response -- e.g. increase in metabolic rate following eating. It is assumes that the reduced thermogenic response is an impairment in the obese. If anything, this aspect of physiology or metabolism is maintained despite severe restriction and malnutrition.

Concluding Thoughts

This post turned out a bit longer than I had intended, and there's nothing all that monumental about it. The subject numbers are small and the variability of various factors within those numbers is substantial.

However inasmuch as we can glean anything from this, even following significant starvation to the point of emaciation, once a person is refed, the adaptive metabolic slowdown is reversed to a large extent. This reversal seems to be less complete for those who were "previously obese". One of the differences often observed between lean and obese is this ability to "waste" acute excesses in the form of a higher thermic response to food. This does not appear to be at play here with the POs. So why do the POs appear to have a more suppressed metabolic rate compared to controls and "recovered" anorectics who were never obese?

Metabolic Adaptation: The go-to explanation these days is "metabolic adaptation" and for a 5'4" woman beginning at 125 lbs down to 85 lbs (pulling numbers out of the air here folks) the severity and duration of caloric restriction to lose 40 lbs is going to be less than for a 150 lbs woman going down to 85 lbs losing 65 lbs. So this *fits* nicely with the idea of adaptation.

Pre-Existing Condition: An alternative explanation, one that was bandied about in older literature but seems to have fallen by the wayside, is that the obese may be predisposed to that condition due to having an inherently lower metabolic rate. This notion was discarded mostly on the basis that the obese have higher metabolic rates, but this is due to weighing more and having to sustain that additional tissue, yes, even the fat tissue requires energy to move! So it is plausible that those who began as obese (defined as 20% over ideal weight in this paper) got that way because they DID have a "slow metabolism" in the first place.

So I'm going to leave it at this for the time being. If anyone out there is aware of any prospective studies that measured metabolic rates in kids and looked at adult rates of overweight and obesity 10-15 yrs down the line, I'd love to get my paws on such a study's results! It's really the only way to know with some degree of certainty. If not, I hope NuSI has a minion reading here and takes note. Since they are measuring energy expenditure and focusing on calories after all, such a study would be a good use for those millions, It may actually produce information that will help people avoid obesity in the first place.